Analysis of the activation profile of dendritic cells derived from the bone marrow of interleukin-12/interleukin-23-deficient mice
| Autor: | Cláudia Augusta Zago, Momtchilo Russo, Luciana Vieira de Moraes, Claudio Romero Farias Marinho, Karina R. B. Bastos, Maria Regina D'Império Lima, José M. Alvarez |
|---|---|
| Rok vydání: | 2005 |
| Předmět: |
Lipopolysaccharide
Immunology Lymphocyte Activation Nitric Oxide Interleukin-23 Immunophenotyping Nitric oxide Interferon-gamma Mice chemistry.chemical_compound Bone Marrow Transforming Growth Factor beta Interleukin 23 medicine Animals Immunology and Allergy Interferon gamma Cells Cultured Cell Proliferation Mice Knockout biology Interleukins Interleukin Dendritic Cells Original Articles Transforming growth factor beta Interleukin-12 Molecular biology Mice Inbred C57BL medicine.anatomical_structure chemistry Interleukin-23 Subunit p19 biology.protein Interleukin 12 Bone marrow medicine.drug |
| Zdroj: | Immunology. 114:499-506 |
| ISSN: | 1365-2567 0019-2805 |
| Popis: | We have previously shown that macrophages from interleukin (IL)-12p40 gene knockout (IL-12/IL-23-/-) mice have a bias towards the M2 activation profile, spontaneously secreting large quantities of transforming growth factor-beta1 (TGF-beta1) and producing low levels of nitric oxide (NO) in response to lipopolysaccharide (LPS) and interferon-gamma (IFN-gamma). To verify whether the activation profile of dendritic cells (DCs) is also influenced by the absence of IL-12/IL-23, bone marrow-derived DCs from IL-12/IL-23-/- and C57BL/6 mice were evaluated. At first we noticed that approximately 50% of the C57BL/6 DCs were dead after LPS-induced maturation, whereas the mortality of IL-12/IL-23-/- DCs was < 10%, a protective effect that diminished when recombinant IL-12 (rIL-12) was added during maturation. Similarly to macrophages, mature IL-12/IL-23-/- DCs (mDCs) produced higher levels of TGF-beta1 and lower levels of NO than C57BL/6 mDCs. NO release was IFN-gamma-dependent, as evidenced by the poor response of IFN-gamma-/- and IL-12/IL-23-/-IFN-gamma-/- mDCs. Nevertheless, IFN-gamma deficiency was not the sole reason for the weak NO response observed in the absence of IL-12/IL-23. The high level of TGF-beta1 secretion by IL-12/IL-23-/- mDCs could explain why exogenous IFN-gamma partially restored the NO production of IFN-gamma-/- mDCs, while IL-12/IL-23-/- IFN-gamma-/- mDCs remained unresponsive. We also showed that CD4+ T-cell proliferation was inhibited by C57BL/6 mDCs, but not by IL-12/IL-23-/- mDCs. IFN-gamma and NO appear to mediate this antiproliferative effect because this effect was not observed in the presence of mDCs from IFN-gamma-/- or IL-12/IL-23-/- IFN-gamma-/- mice and it was attenuated by aminoguanidine. We conclude that the presence of IL-12/IL-23 during LPS-induced maturation influences the activation profile of DCs by a mechanism that is, only in part, IFN-gamma dependent. |
| Databáze: | OpenAIRE |
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